Can dapagliflozin with or without saxagliptin improve symptoms of kidney disease in patients with type 2 diabetes?

This study examined if dapagliflozin (Farxiga) and saxagliptin (Onglyza) improved symptoms of kidney disease in patients with type 2 diabetes and kidney disease. The authors concluded that dapagliflozin with or without saxagliptin reduced kidney disease symptoms and lowered blood glucose levels in these patients.

Type 2 diabetes (T2D) is associated with an increased risk of kidney disease. Drugs that help to lower blood glucose levels can also reduce symptoms of kidney disease. One class of drug, called sodium-glucose co-transporter-2 (SGLT2) drugs, reduce blood glucose levels and may help improve kidney function. Another class of drugs called dipeptidyl peptidase-4 inhibitors (DPP-4i), may do the same using a different route. 

Dapagliflozin is a type of SGLT2 drug and saxagliptin is a type of DPP-4i drug. Studies suggest that the two drugs may boost each other’s effects on kidney function and blood glucose levels. However, it is not known if they do so for kidney function in patients with long-term kidney disease.

This study recruited 461 patients with T2D and long-term kidney disease. Patients received either a placebo (148 patients), dapagliflozin alone (145 patients) or dapagliflozin and saxagliptin (155 patients).  Patients were followed for an average of 24 weeks.

Albumin and creatinine are two proteins that can be found in urine. A high ratio of albumin to creatinine (A/C) can indicate kidney disease. After 24 weeks, the A/C ratio of patients decreased by 21% in the dapagliflozin group and by 38% in the dapagliflozin and saxagliptin group, compared to the placebo group. 

After 24 weeks, patients taking dapagliflozin had a 1.9 times higher chance of lowering their A/C ratio by over 30% and a 3 times higher chance after taking dapagliflozin and saxagliptin.

After 24 weeks, HbA1c (average blood glucose over the past 3 months) was reduced by 0.2% in the dapagliflozin group and 0.6% in the dapagliflozin and saxagliptin group compared to placebo. 10.3% of the placebo group reduced their HbA1c levels below 7%. This was compared to 15.0% of the dapagliflozin group and to 35.1% of the dapagliflozin and saxagliptin group.

55% of the placebo group, 54% of the dapagliflozin group and 68% of the dapagliflozin and saxagliptin group experienced side effects. Dangerously low blood glucose (hypoglycemia) was experienced by 20% of the placebo group, 24% of the dapagliflozin group and 33% of the dapagliflozin and saxagliptin group. Kidney side effects were experienced by 4% of the placebo group, 3% of the dapagliflozin group and 7% of the dapagliflozin and saxagliptin group.

The authors concluded that dapagliflozin and saxagliptin improved kidney function and blood glucose levels in patients with T2D and long-term kidney disease.  

The manufacturer of dapagliflozin and saxagliptin, AstraZeneca, funded this study. This study was limited by the absence of a saxagliptin only group and the short follow-up period.